Ammonium Chloride → 6-(2-Amino-pyrimidin-4-yloxy)-benzofuran-3-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

HRID 556360ノート

反応式

HRID 556360 の反応式
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].C[Al](C)C.C[O:18][C:19]([C:21]1[C:25]2[CH:26]=[CH:27][C:28]([O:30][C:31]3[CH:36]=[CH:35][N:34]=[C:33]([NH2:37])[N:32]=3)=[CH:29][C:24]=2[O:23][CH:22]=1)=O.[NH4+].[Cl-]>C1(C)C=CC=CC=1.C1COCC1>[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:19]([C:21]2[C:25]3[CH:26]=[CH:27][C:28]([O:30][C:31]4[CH:36]=[CH:35][N:34]=[C:33]([NH2:37])[N:32]=4)=[CH:29][C:24]=3[O:23][CH:22]=2)=[O:18])=[CH:4][C:3]=1[C:9]([F:10])([F:11])[F:12]

参加物

7

反応物 4

HCID 25517Ammonium ChlorideHCID 753774-Fluoro-3-(trifluoromethyl)anilineHCID 16682925TrimethylaluminumHCID 575564496-(2-Amino-pyrimidin-4-yloxy)-benzofuran-3-carboxylic acid methyl ester

生成物 1

HCID 247627956-(2-Amino-pyrimidin-4-yloxy)-benzofuran-3-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
10 °C

実験手順

In a dried vessel, 108 mg (0.60 mMol) 4-fluoro-3-trifluoromethyl-aniline are dissolved in 10 ml toluene and cooled to 10° C. Then 900 μl Me3Al (2 M in toluene; 1.8 mMol) are added via syringe. After 1 h at rt, a suspension of 171 mg (0.599 mMol) 6-(2-amino-pyrimidin-4-yloxy)-benzofuran-3-carboxylic acid methyl ester (Step 9.6) in 5 ml THF is added and the reaction mixture is stirred for 40 min in an oil bath of 110° C. The solution is cooled in ice and hydrolyzed with 20 ml of a sat. NH4Cl. After 10 min stirring, the mixture is filtered through Celite, the solid washed extensively with EtOAc and water, the aq. phase separated from the filtrate and extracted with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (SiO2; EtOAc) and crystallization from EtOAc/hexane 1:1 gives the title compound: MS: [M+1]+=433; TLC(hexane/EtOAc 1:9): Rf=0.22.

後処理

  1. additionis added
  2. stirringAfter 10 min stirring
  3. filtrationthe mixture is filtered through Celite
  4. washthe solid washed extensively with EtOAc and water
  5. customthe aq. phase separated from the filtrate
  6. extractionextracted with EtOAc
  7. washThe organic layers are washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customColumn chromatography (SiO2; EtOAc) and crystallization from EtOAc/hexane 1:1

出典と根拠

ORDレコード
ord-7dfa513e312c4d0baa155cb6d530615c
出典データセット
uspto-grants-2011_11
特許番号
US08058276B2

反応ノート

読み込み中…